DETAILED CORRESPONDENCE
Application Status
1. The present application is being examined under the pre-AIA first to invent provisions.
2. Applicant’s amendment to the claims filed on 09/16/2026 in response to the Non-Final Rejection mailed on 06/16/2026 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
3. Claims 7-9, 11, 13, 17, 19, 21-24, 26-28, 30-34 and 36 are cancelled.
4. New claims 37-41 are added.
5. Claims 1, 12, 15-16, 18, 20, 25, 35 and 37-41 are pending.
6. Applicant’s remarks filed on 09/16/2026 in response to the Non-Final Rejection mailed on 06/16/2026 have been fully considered and are deemed persuasive to overcome at least one of the rejections and/or objections as previously applied.
The text of those sections of Title 35 U.S. Code not included in the instant action can be found in the prior Office Action.
Information Disclosure Statement
7. The IDSs filed on 07/31/2026, 08/17/2026, and 09/16/2026 have been considered by the examiner and copies of the Form PTO/SB/08 are attached to the office action.
Claim Rejections - 35 USC § 112(b)
8. The rejection of claims 1, 12, 15-16, 18, 20, 25-27, and 30-36 under 35 U.S.C. 112(b) for indefiniteness is withdrawn in view of applicants’ amendment to the claims.
Double Patenting
9. The terminal disclaimers filed on 09/16/2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patent Application Nos. 19/071005, 19/071055, 19/071264, 19/071092, 19/551393, 19/550136, and 18/922889 and U.S. Patent Nos. 12600959, 12037618, 12104184, 12110520, 12123035, 12152262, 9447401, 12195773, 11041149, 11066656, 12091692, 12077791, 12060590, 12054758, 12049652, 12018298, 11952600, and 10865400 have been reviewed and is accepted. The terminal disclaimers have been recorded.
10. The provisional non-statutory double patenting rejections of claims 1, 12, 15-16, 18, 20, 25-27 and 30-36 over pending application nos. 19/071005, 19/071055, 19/071264, 19/071092, 19/551393, 19/550136, and 18/922889 are withdrawn in view of the filing of the terminal disclaimers on 09/16/2026.
11. The non-statutory double patenting rejections of claims 1, 12, 15-16, 18, 20, 25-27 and 30-36 over U.S. Patent Nos. 12600959, 12037618, 12104184, 12110520, 12123035, 12152262, 9447401, 12195773, 11041149, 11066656, 12091692, 12077791, 12060590, 12054758, 12049652, 12018298, 11952600, and 10865400 are withdrawn in view of the filing of the terminal disclaimers on 09/16/2026.
Claim Rejections - 35 USC § 112(a)
12. The written description rejection of claims 26-27, 30-34 and 36 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is withdrawn in view of applicants’ amendment to the claims to cancel claims 26-27, 30-34 and 36.
13. The scope of enablement rejection of claims 26-27, 30-34 and 36 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is withdrawn in view of applicants’ amendment to the claims to cancel claims 26-27, 30-34 and 36.
14. The new matter rejection of claims 26-27 and 30-31 under 35 U.S.C. 112(a) is withdrawn in view of applicants’ amendment to the claims to cancel claims 26-27 and 30-31.
15. The written description rejection of claims 1, 12, 15-16, 18, 20, and 35 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is maintained for the reasons of record and the reasons set forth below. The rejection has been modified in order to address applicant’s amendment to the claims and in order to incorporate new claims 37-41, which is necessitated by applicants’ amendment to the claims to add new claims 37-41.
Claims 1, 12, 15-16, 18, 20, 35, and 37-41 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP 2163.II.A.2.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
MPEP § 2163 further states that “[s]atisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus…Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’ Such correlations may be established ‘by the inventor as described in the specification,’ or they may be ‘known in the art at the time of the filing date.’"
The factors considered in the Written Description requirement are (1) level of skill and knowledge in the art, (2) partial structure, (3) physical and/or chemical properties, (4) functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the (5) method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient." MPEP § 2163.
As amended, claims 1, 12, 15-16, 18, 20, 35, and 37-41 are drawn in relevant part to a polypeptide comprising an amino acid sequence wherein a respective position of the amino acid sequence corresponds to a corresponding position of a reference amino acid sequence, and the reference amino acid sequence consists of reference amino acid residues identified with reference to positions 3-433 of SEQ ID NO: 35; and wherein the amino acid sequence has at least 95% sequence identity to the reference amino acid sequence with the exception of amino acid replacement location at 309, 312, 313, 317, 320, and 324 of the reference sequence. The application does not provide any other mutations and combinations of mutations outside single point mutations that falls within the structure of a polypeptide having 95% sequence identity to the amino acid sequence of SEQ ID NO: 35.
In this case, the specification discloses an actual reduction to practice of the following representative species of the genus of “polypeptides” as encompassed by the claims (i.e. a PH20 polypeptide having hyaluronidase activity with a single point mutation in positions corresponding to positions 3, 5, 8, 9, 11, 12, 14, 15, 16, 17, 18, 19, 20, 22, 23, 24, 26, 27, 28, 35, 36, 37, 39, 41, 42, 43, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 58, 60, 61, 62, 63, 64, 67, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 81, 82, 83, 84, 85, 86, 91, 93, 94, 96, 97, 98, 99, 100, 102, 105, 106, 138, 141, 142, 143, 145, 146, 147, 149, 150, 152, 153, 154, 156, 157, 158, 159, 160, 161, 162, 164, 165, 166, 167, 169, 201, 206, 208, 209, 210, 215, 216, 217, 219, 220, 221, 222, 223, 224, 225, 227, 228, 229, 230, 231, 232, 234, 235, 237, 238, 239, 240, 241, 263, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 276, 278, 279, 280, 281, 287, 288, 290, 291, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 317, 318, 319, 320, 321, 323, 324, 325, 326, 327, 328, 330, 331, 332, 335, 336, 337, 338, 339, 342, 343, 344, 345, 348, 350, 351, 353, 354, 355, 356, 359, 360, 362, 363, 366, 369, 370, 372, 373, 376, 379, 381, 382, 383, 385, 387, 388, 391, 393, 394, 395, 396, 397, 398, 399, 403, 404, 405, 406, 409, 410, 412, 414, 415, 419, 420, 422, 425, 428, 430, 432, and 433 of SEQ ID NO: 35). Other than the above disclosed species there is no other drawings or structural formulas of the infinite polypeptides of any function as encompassed by the claims. As stated above, the breadth of the claims include additional mutations and combinations of mutations of any structure that fall within the genus of the claims.
Regarding the level of skill and knowledge in the art of amino acid modification, MPEP 2144.08.II.A.4.(c) states, "[i]n the area of biotechnology, an exemplified species may differ from a claimed species by a conservative substitution ("the replacement in a protein of one amino acid by another, chemically similar, amino acid... [which] is generally expected to lead to either no change or only a small change in the properties of the protein." Dictionary of Biochemistry and Molecular Biology 97 (John Wiley & Sons, 2d ed. 1989)). The effect of a conservative substitution on protein function depends on the nature of the substitution and its location in the chain. Although at some locations a conservative substitution may be benign, in some proteins only one amino acid is allowed at a given position. For example, the gain or loss of even one methyl group can destabilize the structure if close packing is required in the interior of domains. James Darnell et al., Molecular Cell Biology 51 (2d ed. 1990)."
More specific to the claimed invention, the reference of Zhang (J. Biol. Chem. 284:9433-9442, 2009; cited on PTO-892 mailed on 06/16/2026) teaches that based on homologous sequences, Asp129 was predicted to be an essential catalytic residue and would be critical for catalytic activity of human hyaluronidase 1 [p. 9436, column 2, top and p. 9437, column 2, middle], however, Asp129 was empirically determined to be non-essential because significant activity of an Asp129Asn substitution mutant was retained [p. 9437, column 2, middle].
The reference of Singh et al. (Current Protein and Peptide Science, 2017; cited on PTO-892 mailed on 06/16/2026) reviews various protein engineering methods and discloses that despite the availability of an ever-growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes [see p. 7, column 1, top].
The reference of Zhang et al. (Structure, 2018; cited on PTO-892 mailed on 06/16/2026) discloses that a mutation of a residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide [p. 1475, column 1].
In the Federal Circuit decision, Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337 (Fed. Cir. 2021), the courts found that for broad claims to a nucleic acid encoding a chimeric T cell receptor with a functional requirement to bind a target, “the written description must demonstrate that the applicant made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus”. In the instant case, the claims are drawn to polypeptide of unlimited structure and function, and the specification does not disclose sufficient structural features in the claimed polypeptide sequence associated with any activity to allow an ordinary artisan to distinguish which multiple mutated sequences will result in polypeptides of any activity. While a person skilled in the art might be able to embark on their own research program to find suitable multiply modified polypeptides, the four corners of the written description do not demonstrate possession of such. This analysis is consistent with AbbVie Deutschland GmbH v. Janssen Biotech, Inc., 759 F.3d 1285, 1300 (Fed. Cir. 2014) which required an inventor to show “that one has truly invented the genus, i.e. that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus”.
Given that the specification discloses only a relative few representative species of single amino acid mutations at each of positions 309, 312, 313, 317, 320, and 324 with reference to SEQ ID NO: 35, the specification fails to disclose even a single representative species of the claimed combinations of mutations of the polypeptide, and there is a very high level of unpredictability in the art of amino acid modification, the specification is considered to be insufficient to describe the claimed genus of polypeptides. In this case, the specification at best describes a research plan for making, testing, and identifying those species that are encompassed by the claimed genus of polypeptides, however, a plan for making the claimed invention is not sufficient to show possession at the time of filing. One of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus, and thus, that the applicant was not in possession of the recited genus.
For these reasons, it is the examiner’s position that the specification fails to adequately describe the claimed invention.
RESPONSE TO REMARKS: Applicants’ remarks filed on 09/16/2026 have been fully considered by the examiner. Applicants in summary contend that the specification describes polypeptides with combinations of multiple replacements beyond isolated single mutants, the disclosed amino acid sequence framework and structure-function discussion within the specification supply adequately identifying characteristics of the genus, the experimental examples provided throughout the specification support the genus through the structural variation and combinatorial guidance conveyed therein and the prior art references cited by the Office Action as evidence fail to establish that the applicants’ specification does not descrive the multiple replacement polypeptide species falling within the genus of amended claim 1.
These arguments are found to be not persuasive because MPEP 2163.II.A.3.(a).ii states "when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the genus]." See Enzo Biochem, S2S F.Sd at 966, 63 USPQ2d at 1615; Noelle V. Ledermon, 355 F.3d 1343,1350, 69 USPQ2d 1508,1514 (Fed. Cir. 2004) (Fed. Cir. 2004)". In the instant case, while applicants point to tables 3, 5, 9, and 10 to support embodiments to include multiple amino acid replacements and provides guidance for doing so, this data shows single substitution data where substitutions are tolerated; however, it fails to show results for polypeptides having multiple modifications. While one skilled in the art may be able to make predictions about the effect of multiple modifications on hyaluronidase activity, this at most describes a research plan rather than showing the inventors where in fact in possession of the full scope of the invention as claimed. The examiner’s position is further supported by the Federal Circuit decision in Novozymes v. Dupont, July 2013 (cited herein). The court found that the claims to a narrowly recited specific alpha-amylase at a single amino acid position was not adequately described or supported by the written description as the application provided only a generalized guidance listing several variables that might, in some combination, lead to a useful result. In the instant case, Tables 3, 9, and 10 of single point mutations provided by applicants to support the claimed combinations of mutations in the claims provides “only generalized guidance listing several variables that might, in some combination, lead to a useful result”. While the application does disclose “combinations thereof” of the single point mutations, the claimed combination is only one among a list of thousands of possible combinations that could be made from the single point mutations disclosed in Tables 3, 5, 9, and 10.
16. The scope of enablement rejection of claims 1, 12, 15-16, 18, 20, and 35 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is maintained for the reasons of record and the reasons set forth below. The rejection has been modified in order to address applicant’s amendment to the claims and in order to incorporate new claims 37-41, which is necessitated by applicants’ amendment to the claims to add new claims 37-41.
Claims 1, 12, 15-16, 18, 20, 35, and 37-41 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while enabling for a PH20 polypeptide having hyaluronidase activity with a single point mutation in positions corresponding to positions 3, 5, 8, 9, 11, 12, 14, 15, 16, 17, 18, 19, 20, 22, 23, 24, 26, 27, 28, 35, 36, 37, 39, 41, 42, 43, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 58, 60, 61, 62, 63, 64, 67, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 81, 82, 83, 84, 85, 86, 91, 93, 94, 96, 97, 98, 99, 100, 102, 105, 106, 138, 141, 142, 143, 145, 146, 147, 149, 150, 152, 153, 154, 156, 157, 158, 159, 160, 161, 162, 164, 165, 166, 167, 169, 201, 206, 208, 209, 210, 215, 216, 217, 219, 220, 221, 222, 223, 224, 225, 227, 228, 229, 230, 231, 232, 234, 235, 237, 238, 239, 240, 241, 263, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 276, 278, 279, 280, 281, 287, 288, 290, 291, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 317, 318, 319, 320, 321, 323, 324, 325, 326, 327, 328, 330, 331, 332, 335, 336, 337, 338, 339, 342, 343, 344, 345, 348, 350, 351, 353, 354, 355, 356, 359, 360, 362, 363, 366, 369, 370, 372, 373, 376, 379, 381, 382, 383, 385, 387, 388, 391, 393, 394, 395, 396, 397, 398, 399, 403, 404, 405, 406, 409, 410, 412, 414, 415, 419, 420, 422, 425, 428, 430, 432, and 433 of SEQ ID NO: 35, does not reasonably provide enablement for all polypeptides as encompassed by the claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
“The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue.” In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976). Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)) as follows: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01(a). The Factors considered to be most relevant to the instant rejection are addressed in detail below.
The breadth of the claims: As amended, claims 1, 12, 15-16, 18, 20, 35, and 37-41 are drawn in relevant part to a polypeptide comprising an amino acid sequence wherein a respective position of the amino acid sequence corresponds to a corresponding position of a reference amino acid sequence, and the reference amino acid sequence consists of reference amino acid residues identified with reference to positions 3-433 of SEQ ID NO: 35; and wherein the amino acid sequence has at least 95% sequence identity to the reference amino acid sequence with the exception of amino acid replacement location at 309, 312, 313, 317, 320, and 324 of the reference sequence. The application does not provide any other mutations and combinations of mutations outside single point mutations that falls within the structure of a polypeptide having 95% sequence identity to the amino acid sequence of SEQ ID NO: 35.
The state of the prior art; The level of one of ordinary skill; and The level of predictability in the art: As noted above, the structure and function of the claimed polypeptide is unlimited.
Regarding the level of skill and knowledge in the art of amino acid modification, MPEP 2144.08.II.A.4.(c) states, "[i]n the area of biotechnology, an exemplified species may differ from a claimed species by a conservative substitution ("the replacement in a protein of one amino acid by another, chemically similar, amino acid... [which] is generally expected to lead to either no change or only a small change in the properties of the protein." Dictionary of Biochemistry and Molecular Biology 97 (John Wiley & Sons, 2d ed. 1989)). The effect of a conservative substitution on protein function depends on the nature of the substitution and its location in the chain. Although at some locations a conservative substitution may be benign, in some proteins only one amino acid is allowed at a given position. For example, the gain or loss of even one methyl group can destabilize the structure if close packing is required in the interior of domains. James Darnell et al., Molecular Cell Biology 51 (2d ed. 1990)."
More specific to the claimed invention, the reference of Zhang (J. Biol. Chem. 284:9433-9442, 2009; cited on PTO-892 mailed on 06/16/2026) teaches that based on homologous sequences, Asp129 was predicted to be an essential catalytic residue and would be critical for catalytic activity of human hyaluronidase 1 [p. 9436, column 2, top and p. 9437, column 2, middle], however, Asp129 was empirically determined to be non-essential because significant activity of an Asp129Asn substitution mutant was retained [p. 9437, column 2, middle].
The reference of Singh et al. (Current Protein and Peptide Science, 2017; cited on PTO-892 mailed on 06/16/2026) reviews various protein engineering methods and discloses that despite the availability of an ever-growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes [see p. 7, column 1, top].
The reference of Zhang et al. (Structure, 2018; cited on PTO-892 mailed on 06/16/2026) discloses that a mutation of a residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide [p. 1475, column 1].
The evidence of record demonstrates that identifying which of the members of the polypeptides genus of any activity was not known in the art, and one of skill in the art would recognize a high level of unpredictability in the art of amino acid modification.
The amount of direction provided by the inventor and The existence of working examples: The specification discloses the following working examples of polypeptides of any function, i.e. a PH20 polypeptide having hyaluronidase activity with a single point mutation in positions corresponding to positions 3, 5, 8, 9, 11, 12, 14, 15, 16, 17, 18, 19, 20, 22, 23, 24, 26, 27, 28, 35, 36, 37, 39, 41, 42, 43, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 58, 60, 61, 62, 63, 64, 67, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 81, 82, 83, 84, 85, 86, 91, 93, 94, 96, 97, 98, 99, 100, 102, 105, 106, 138, 141, 142, 143, 145, 146, 147, 149, 150, 152, 153, 154, 156, 157, 158, 159, 160, 161, 162, 164, 165, 166, 167, 169, 201, 206, 208, 209, 210, 215, 216, 217, 219, 220, 221, 222, 223, 224, 225, 227, 228, 229, 230, 231, 232, 234, 235, 237, 238, 239, 240, 241, 263, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 276, 278, 279, 280, 281, 287, 288, 290, 291, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 317, 318, 319, 320, 321, 323, 324, 325, 326, 327, 328, 330, 331, 332, 335, 336, 337, 338, 339, 342, 343, 344, 345, 348, 350, 351, 353, 354, 355, 356, 359, 360, 362, 363, 366, 369, 370, 372, 373, 376, 379, 381, 382, 383, 385, 387, 388, 391, 393, 394, 395, 396, 397, 398, 399, 403, 404, 405, 406, 409, 410, 412, 414, 415, 419, 420, 422, 425, 428, 430, 432, and 433 of SEQ ID NO: 35. Other than these working examples, the specification fails to disclose any other working examples of polypeptides having multiple replacements of any activity as encompassed by the claims.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure: In the Federal Circuit decision of Idenix Pharmaceuticals LLC v. Gilead Sciences Inc., 941 F.3d 1149, 1156 (Fed. Cir. 2019), the court stated that “the key enablement question is whether a person of ordinary skill in the art would know, without undue experimentation, which [species] would be effective….because of the many thousands of [species] which need to be screened for…efficacy, the quantity of experimentation needed is large and weighs in favor of non-enablement.” In the instant case, the number is not thousands but much higher, and as such, the quantity of experimentation would be many orders of magnitude more than that in Idenix.
While methods for modifying the amino acid sequence of a polypeptide were known before the effective filing date, it was not routine in the art to screen by a trial and error process for all polypeptides of any activity with respect to a reference polypeptide comprising SEQ ID NO: 35 as broadly encompassed by the claims.
In view of the overly broad scope of the claims, the lack of guidance and working examples provided in the specification, the high level of unpredictability, and the state of the prior art, undue experimentation would be necessary for a skilled artisan to make and use the entire scope of the claimed invention. Applicants have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
RESPONSE TO REMARKS: Applicants’ remarks filed on 09/16/2026 have been fully considered by the examiner. Applicants in summary contend that the specification expressly enables multiple modifications and describes iterative introduction and combination of identified modifications.
These arguments are found to be not persuasive because while applicants point to tables 3, 5, 9, and 10 to support embodiments to include multiple amino acid replacements and provides guidance for doing so, this data shows single substitution data where substitutions are tolerated; however, it fails to show results for polypeptides having multiple modifications. While one skilled in the art may be able to make predictions about the effect of multiple modifications on hyaluronidase activity, the claims are broad and the number of distinct peptides having the combination of mutations is large. As set forth in the PTAB decision in Merck v. Halozyme (PGR2025-00006) (cited herein), while skill in the art is very high and prior art in the field was developed, there was evidence that homology modeling at the time of the invention was not yet reliable [see p. 103 of the PGR decision]. The examiner’s position is further supported by the Federal Circuit decision in Novozymes v. Dupont, July 2013 (cited herein). The court found that the claims to a narrowly recited specific alpha-amylase at a single amino acid position was not adequately described or supported by the written description as the application provided only a generalized guidance listing several variables that might, in some combination, lead to a useful result. In the instant case, Tables 3, 9, and 10 of single point mutations provided by applicants to support the claimed combinations of mutations in the claims provides “only generalized guidance listing several variables that might, in some combination, lead to a useful result”. While the application does disclose “combinations thereof” of the single point mutations, the claimed combination is only one among a list of thousands of possible combinations that could be made from the single point mutations disclosed in Tables 3, 5, 9, and 10, and the amount of experimentation needed to make and test each possible combination of mutations as encompassed by the claims would be unnecessarily undue.
17. The new matter rejection of claims 12, 15-16, 18, and 20 under 35 U.S.C. 112(a) as failing to comply with the written description requirement is maintained for the reasons of record and the reasons set fort below. The rejection has been modified in order to incorporate claims 1, 25, 35, and 37-41, which is necessitated by applicants’ amendment to the claims.
Claims 1, 12, 15-16, 18, 20, 25, 35, and 37-41 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
MPEP § 2163.II.A.3.(b) states, “when filing an amendment an applicant should show support in the original disclosure for new or amended claims”. See also MPEP 714.02. MPEP § 2163.II.A.3.(b) further states, “[i]f the originally filed disclosure does not provide support for each claim limitation, or if an element which applicant describes as essential or critical is not claimed, a new or amended claim must be rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112, para. 1, as lacking adequate written description”. According to MPEP § 2163.I.B, “While there is no in haec verba requirement, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure” and “The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117”.
Claims 1, 12, 15-16, 18, 20, 25, 35, and 37-41 recite specific combinations of amino acid replacements. Applicant fails to show support for the specific combinations of amino acid replacements as recited in claims 1, 12, 15-16, 18, 20, 25, 35, and 37-41. While the original application discloses single amino acid variants of most of the amino acids of the sequence of amino acids and generically discloses “combinations of modifications” and “one or more amino acid replacements, there is no apparent descriptive support for the specific combinations recited in claims 1, 12, 15-16, 18, 20, 25, 35, and 37-41 in the original application as filed. In the absence of descriptive support, the recitation of these specific combinations is considered to introduce new matter into the claims.
RESPONSE TO REMARKS: The examiner has reviewed the response filed on 09/16/2026 and found no traversal of the new matter rejection of record; however, in the interest of compact prosecution, the remarks set forth above regarding the written description rejection are applicable to the new matter rejection above.
Conclusion
18. Status of the claims:
Claims 1, 12, 15-16, 18, 20, 25, 35 and 37-41 are pending.
Claims 1, 12, 15-16, 18, 20, 25, 35 and 37-41 are rejected.
No claims are in condition for an allowance.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL J HOLLAND whose telephone number is (571)270-3537. The examiner can normally be reached Monday to Friday from 8AM to 5PM.
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/PAUL J HOLLAND/Primary Examiner, Art Unit 1656
